KR20140031892A - Use of an agent consisting of antibodies and/or insulin-like growth factor antagonists - Google Patents

Abstract

The present invention relates to the use of a composition selected from the group consisting of antibodies, antibody fragments, insulin like growth factor antagonists, toll like receptor antagonists and mixtures thereof for the treatment or prevention of certain diseases.

Description

Use of an agent consisting of antibodies and / or insulin-like growth factor antagonists

The present invention relates to the use of the therapeutic or prophylactic treatment of certain diseases of a drug selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof.

Human diseases are currently being treated with various therapeutic agents. Likewise, a number of drugs are used to prevent disease. Despite these various treatment options, new therapeutic and prophylactic drugs are constantly required to develop new treatment methods and to improve and further improve known treatment methods.

To date, it has been known that antibodies to toxins can be used for the treatment of certain diseases (eg, chronic pain syndrome). Endotoxins are breakdown products of bacteria that can trigger numerous physiological reactions in the body. Antibodies to endotoxins are also included in the natural antibody spectrum of bovine colostrum.

Oral immunoglobulins from plasma, colostrum, milk, egg or cell culture are known for the treatment and prevention of physiologically correlated chronic pain (DE 195 48 221 C1).

W.G. Struff and G. Sprotte (Int. J. Clin. Pharmacol. Ther., 2007 Apr; 45 (4): 193-202) disclose biotechnical standards, pharmacodynamic and pharmacokinetic properties and methods of treatment of cow colostrum.

W.G. Struff and G. Sprotte (Int. J. Clin. Pharmacol. Ther., 2008 May; 46 (5): 211-25) disclose clinical studies of cow colostrum.

A.M. Waaga-Gasser et al (Int. J. Clin. Pharmacol. Ther., 2009 Jul; 47 (7): 421-33) disclose that oral immunoglobulins from cow colostrum can treat patients with chronic pain syndrome. .

A. Goebel et al. Disclose data showing improved permeability in the gastroduodenal region and small intestine in the presence of two chronic pain syndromes (fibromyalgia syndrome and complex regional pain syndrome).

It is therefore an object of the present invention to provide agents which have a positive effect, in particular, which enhance the prevention and / or treatment of certain diseases. Certain diseases herein are diseases selected from group X:

Polyneuropathy, mononeuropathy, autonomic neuropathy, small fiber neuropathy, especially autoimmune diseases, type 1 and type 2 diabetes (diabetes mellitus type I and II), diabetes type A, B, C, D, E, F, G, H, polyclonal gammopathy and / or kidney dysfunctions The above symptoms in

Peripheral nerve compression syndromes (eg, carpal tunnel syndrome), ulnar nerve entrapment syndrome (cubital tunnel syndrome, Morton's) metatarsalgia), Bernardhardt-Roth syndrome (meralgia paraesthetica), thoracic outlet syndrome (TOS)

Arthrosis other than osteoarthrosis, especially activated arthrosis, primary arthrosis, and secondary arthrosis.

Enthesiopathies in collagenoses

Achilles tendon pain

Calcanodynia and heel spur

Periarthritis humero-scapularis

Tietze's syndrome (sternoclavicular joint arthropathy)

Arthropathy of the iliosacral joint

Myoarthropathy of the masticatory apparatus, craniomandibular dysfunction

Cervical spine syndrome after deceleration trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

Asthma

Interstitial cystitis (painful bladder syndrome)

Food allergy

Allergy to light, especially polymorphic photodermatosis

Mucositis, in particular, oral mucositis and / or mucositis after radiation therapy (radiogenic mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

Mucosal ulcers in Behcet's syndrome

Mucosal erosions in pemphigus vulgaris

Mucosal lesions in scleroderma

Mucosal lesions in Sjogen's syndrome

Migraine without aura

Cardiovascular diseases.

Another (partial) object of the present invention is to provide a composition which in particular enhances the prophylaxis and / or treatment of a disease selected from the group Y below. The disease is as follows:

Irritable bowel syndrome

Reactive arthritis

Ulcerative colitis

Crohn's disease

Graft-versus-host disease.

The object of the invention is achieved by the independent claims.

Summary of the Invention

One embodiment of the invention

Multiple neuropathy, mononeuropathy, autonomic neuropathy, fibrofibropathy, in particular autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E, F, G, H, The above symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis

-Adjunctival disease in collagenoses

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche Syndrome

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

Antibodies, antibody fragments, insulin-like growth factor antagonists for the treatment or prevention of diseases anatomically pathologically correlated with diseases selected from group X consisting of cardiovascular diseases ), Toll-like receptor antagonists and mixtures thereof.

In the case of asthma above, the drug does not include insulin-like growth factor antagonists and toll-like receptor antagonists,

(i.) the treatment or prevention is performed orally and / or

(ii.) The antibody and / or antibody fragment targets at least 5 wt.%, preferably 10 wt.% of Gram negative bacteria relative to the total antibody content of the drug.

Another embodiment of the present invention is

Multiple neuropathy, mononeuropathy, autonomic neuropathy, fibrofibropathy, in particular autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E, F, G, H, The above symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis;

-Adjunctival disease in collagenoses

-Lateral epicondylitis

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche syndrome (arthrosis of the clavicle joint)

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

Cardiovascular Disease

Irritable bowel syndrome

-Reactive arthritis

-Ulcerative colitis

Crohn's disease

In treating or preventing a disease selected from the X and Y groups consisting of graft-versus-host disease, the antibody for treating or preventing the apoptosis of mononuclear cells that take up lipopolysaccharide, thereby treating or preventing the disease , Antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists, and mixtures thereof.

In our study, we found that, surprisingly, a common mechanism could affect the diseases mentioned.

Our studies surprisingly show that the diseases mentioned above are caused and persist in part by deficiencies in biological barriers to bacterial toxins, especially endotoxins. In addition to defects in the mechanical barrier of the gut mucosa (Goebel A. et al., Rheumatology, 2008), defects in the treatment of immune cells of toxins recognized as antigens (Waaga-Gasser AM et al, International Journal of Clinical Ph) Palology and Therapeutics, 2009), may also be mentioned as other preconditions that exacerbate the symptoms of the diseases mentioned. However, the fact that this mechanism also applies to diseases of the X and Y groups is not expected from the background of the art to which this invention belongs.

Defective treatment of bacterial antigens constitutes "scheduled cell death", ie, apoptosis, which does not begin with a sufficient amount of mucosal immune cells (especially mononuclear cells) that swallow the antigen. Apoptosis usually results in partial neutralization of toxins in the immune barrier of the digestive tract.

In patients with defects in mechanical and immunological barrier action, compared to patients with intact barrier action, excess immune cells are present in venous blood, which continues to present bacterial toxins from the digestive tract. These immune cells do not enter the normally expected apoptosis after swallowing the toxin. Close correlation with this finding in the cellular immune system is that a constellation of defects of a typical human immune response in this disease mechanism is found in the serum or plasma of the patient.

Surprisingly, the studies performed will demonstrate the therapeutic and / or prophylactic effects of drugs comprising antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists in patients with one or more of the listed diseases. Can be. In addition to idiopathic pain syndrome, patients in this study usually had one or more listed diseases (co-morbidities).

The results of clinical studies conducted using the drug according to one embodiment of the present invention show for the first time the healing action in patients with comorbidities of the present study. Furthermore, it is surprisingly demonstrated for the first time that endotoxins may play a pathogenic role in the induction and maintenance of chronic (to date idiopathic) pain syndromes, as well as in typical symptoms of known diseases.

One embodiment of the invention

Multiple neuropathy, mononeuropathy (possibly without central trigeminal neuralgia), autonomic neuropathy, fibrofibropathy, especially autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C , D, E, F, G, H, the above-mentioned symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis; In particular, activated arthrosis, primary arthrosis, secondary arthrosis

-Adjunctival disease in collagenoses

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche Syndrome

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

A drug selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof for the treatment or prevention of diseases selected from group X consisting of cardiovascular diseases,

In the case of asthma above, the drug does not include insulin-like growth factor antagonists and toll-like receptor antagonists,

1. The treatment or prophylaxis is performed orally and / or

2. The antibody and / or antibody fragment is a drug which targets at least 5 wt.%, Preferably 10 wt.% Of Gram negative bacteria relative to the total antibody content of the drug.

In other or all of the above descriptions, it may be desirable for the drug to be used in accordance with the present invention to not include insulin-like growth factor antagonists and toll-like receptor antagonists.

In the context of the present invention, an antibody or antibody fragment is a protein of the globulin class having at least one specific antigen-binding site (paratope). Antibodies in vivo (in a response to a specific antigen in vivo ) .

Drugs which, after being introduced into humans and animals in vivo, elicit specific immune responses, especially antibody-forming responses, which are expressed by themselves, are called antigens.

An antigen may have several epitopes (antigen crystals, antigen-binding sites) capable of binding other antibodies. For this reason, in vivo, even when immunized with a single antigen, a mixture of antibodies (polyclonal antibodies) always having different specificities is formed. In contrast, a single mono- or bispecificity antibody is called a monoclonal antibody.

Certain antigens generally lead to the formation of very few, specifically matched antibodies that recognize only this foreign substance through specific non-covalent bonds.

An antigen herein is, in particular, a microorganism (species) or part thereof.

In the context of this specification, the description set forth above is intended to aid understanding as to the meaning of diseases that are anatomically pathologically correlated. Anatomical pathological correlations refer to cases where detectable biologic damage is believed to be the cause of the symptoms of a particular disease. Such biological damage can be inflamed and / or caused by pathological metabolic conditions. It should be noted that the definition of anatomical pathological correlations described above also does not explicitly include the physiological situation of the mechanisms of action disclosed and described herein, i.e. the presence of toxin-loading monocytes. This knowledge did not exist in the art to which the present invention pertains and therefore is not known as an anatomical pathological correlation.

Surprisingly, a drug selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists can be used to treat and / or treat patients with one or more diseases listed in group X and / or group Y. It has a prophylactic effect.

The use according to one embodiment of the present invention has the following advantages: While the possibility of side effects is lower than conventional therapies, the use according to the invention is very effective.

It has been found that in a use according to one embodiment of the present invention another positive effect improves the sleep quality and mood of sick patients. It has also been found that antibodies can sometimes help the healing process.

Reactive arthritis described in group Y is an inflammatory disease of large joints (monoarthritis) or spinal joints (spondylarthritis / spondyloarthropathy; spondylarthropathy) in individuals with bacterial infection of the digestive tract or urethra. These pathogens themselves do not cause inflammation of the joints, but are "indirect" consequences of infections where bacterial antigens enter the joints by translocation and "reactively" trigger inflammation in the bloodstream at the site of infection.

Use according to the invention / The drug according to the invention is patient friendly for oral treatment and / or prophylaxis.

Preferred embodiments according to the invention relate to the invention, preferably to the drugs according to the above-mentioned embodiments, characterized in that they are suitable for oral treatment or prophylaxis.

After oral ingestion, the ingested drug or antibody and / or antibody fragments reach their specific antigen (also toxin) via the digestive tract and arrive at the mucosa that is defective in barrier function. In the mucosa they deliver antibody- or antigen-specific biological signals for apoptosis to immune cells that have already swallowed endotoxins. Insulin-like growth factor antagonists, which may alternatively or additionally also be used, contribute to the transmission of apoptosis signals.

Oral (digestive tract) treatment has a variety of advantages over parenteral dosage forms (e.g., intravenous, intramuscular, subcutaneous). In terms of use according to the present invention, oral administration results in the drug (or antibody and / or antibody used). Fragments) do not enter the blood circulation, which significantly reduces side effects. It is digested in the gastrointestinal tract, like other (food) proteins, before entering the living organism in simple amino acid form. In contrast, a parenterally administered protein (eg, with plasma or serum) is regulated by the immune system in relation to tolerance or defense. Human plasma or serum proteins have an acceptable risk of side effects and are only allowed parenterally. Oral use, on the other hand, allows for the use of xenogeneic antibodies that are naturally tolerated by the protein in the digestive tract and are also economically desirable. In addition, oral therapy forms are preferred and convenient for patients. No contact (eg, vein) is required for administration. Compared with other dosage forms, improved medication compliance and increased likelihood of onset of action are expected in this regard.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are characterized in that the antibodies and / or antibody fragments at least partially target Gram negative bacteria. This significantly increases the action of the drug.

Gram-negative bacteria are preferably Streptobacillus moniliformis, meningococcus, Chlamydophila, chlamydia, spirochetes, cyanobacteria, proteo Enterobacteriaceae (E. coli, Salmonella, Shigella, Klebsiella, Proteus, Enterobacter), Pseudomonas bacteria bacteria, Legionella bacteria, Neisseria bacteria, Rickettsia bacteria, Pasteurella multocida bacteria and Bacteroidetes strain Is selected from.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are at least partially monoclonal antibodies, polyclonal antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists. Raw antibodies, primatized monoclonal antibodies, antibody fusion proteins, antibody fragments, conjugated antibodies, radiolabeled antibodies, bispecific antibodies and / or monoclonal intrabodies ) In the form of an antibody.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists, at least in part, murine, chimeric, humanized And monoclonal antibodies selected from the group consisting of human and human monoclonal antibodies.

Very particularly preferably, in view of the use according to the invention, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist are at least partially in the form of human monoclonal antibodies. Human monoclonal antibodies have the lowest immunogenicity (property causing immune system called immune response) compared to murine, chimeric and humanized monoclonal antibodies. Murine monoclonal antibodies show the highest immunogenicity.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, comprise or are above immunoglobulin A, immunoglobulin D, immunoglobulin E, immunoglobulin M, immunoglobulin G and / or immunoglobulin Y Characterized by consisting of immunoglobulin (s).

Very particularly preferably, in terms of particularly preferred uses according to the invention, the drug comprises immunoglobulin Y (IgY).

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are obtained at least partially, preferably completely from algae, antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists It is characterized by.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are those obtained at least partially, preferably completely from chicken, antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists It features.

Drugs used according to the invention, at least in part, preferably completely, from birds, in particular chickens, have the advantage of providing surprisingly high compliance, inter alia, when administered to humans and / or animals. In addition, these drugs which are preferably used according to the present invention can be prepared in high purity (drug concentration) and, thus, in therapeutic use, can relatively lower the dose actually used (sum of drug and other ingredients). As a result, the burden on the patient associated with drug intake is reduced. In addition, antibodies from birds, especially antibodies from chickens, can be produced in an economically advantageous manner because of the large animal population.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are at least partially monoclonal antibodies, polyclonal antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists. Raw antibodies, primatized monoclonal antibodies, antibody fusion proteins, antibody fragments, conjugated antibodies, radiolabeled antibodies, bispecific antibodies and / or monoclonal intrabodies ) In the form of an antibody and characterized in that the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist are at least partially, preferably completely obtained from chicken.

In our studies, it has been surprisingly found that when antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists are at least partially obtained from chickens, particularly good results are obtained when using the drug according to the invention. It has been found that the compliance according to the invention is surprisingly better when used in patients than when used in mammals, particularly livestock.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, comprise antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists at least partially from liquid and / or dry egg yolk. It is characterized by the obtained.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, comprise at least partially solid egg yolk powder, preferably antibodies, antibody fragments, insulin-like growth factor antagonists and / or toll-like receptor antagonists. It is characterized in that it is obtained from dry degreasing egg yolk powder.

Degreasing egg yolk powder is obtained by standard processes (removing fat from the dry yolk powder), preferably using hexane. After removing fat, the skim egg yolk powder is dried again.

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are obtained, at least in part, from an antibody, an antibody fragment, an insulin-like growth factor antagonist and / or a toll-like receptor antagonist from dry, degreasing egg yolk powder. It is characterized by. In the above, skim egg yolk powder is obtained from chicken eggs.

In our study, which we conducted, it was surprisingly found that the extended antibody spectrum from natural biological sources, especially from egg yolk, was particularly active. The source of the drug used according to the invention can be sensed regularly from co-substances with the drug. Thus, drugs obtained from egg yolk are commonly used, for example, lipoproteins such as HDL and LDL; And water-soluble proteins of egg yolk such as α-livetin (80 kDa), β-rivetin (45 kDa) and / or γ-rivetin (150 kDa), including most enzymes found in eggs. (Ternes, Acker and Scholtyssek, Ei und Eiprodukte, 1994).

Particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, are characterized in that they are a medicament or a component of a medicament and / or a formulation prepared for administration.

A very particularly preferred drug according to the invention, preferably according to the preferred embodiments described above, is a medicament or a constituent of medicament prepared for administration with colostrum (preferably cow colostrum). It is characterized in that it is a component of phosphorus and / or formulation.

In the present invention, the first milk of the mammal produced in the female mammary gland on the first day is called cow colostrum in order to provide optimal nutrients to the newborn. Cow colostrum is also called pre-milk, colostrum or beastings and includes proteins, enzymes, vitamins, minerals, growth factors, amino acids and antibodies.

In the present invention, medicines or equivalent medical preparations are intended as drugs with the healing or prophylactic properties of human or animal diseases, or by pharmacological, immunological or metabolic action A substance or composition that can be used in the body of a human or animal, or can be administered to a human or an animal, for recovery, correction or impact or to establish a medical diagnosis. Preferably, in the present specification, "medicine" is used as a meaning of a corresponding substance and / or a mixture of corresponding substances in order to be approved under the laws of the manufacture of medicines used in a particular country, particularly preferably the German medicines manufacturing law. I understand. Preferred medications herein also include "orphan medicaments" (orphan drugs), which are subject to simplified approval procedures and are preferably approved under European and / or US law.

Very particularly preferred drugs according to the invention, preferably according to the preferred embodiments described above, consist of pharmaceutical preparations, cosmetic preparations, foodstuffs, food supplements, functional foods, medicines, feed, feed additives and dietary supplements for animals It is characterized in that it is a component of a preparation prepared for administration selected from the group.

According to the present invention, foods and their corresponding newly developed products, in which the degree of nutrition and flavor are purely added to the basics of a particular ingredient, are summarized as "functional foods". As shown in the preparation examples herein, the same meanings, but partially different, the terms nutriceuticals, foodsceuticals and designer foods are used.

In our study, surprisingly, when the drug is a component of a preparation prepared for administration, when the drug contained in the prepared preparation is at least partially obtained from egg yolk of a chicken, preferably chicken, according to the invention, preferably in the stomach It has been found that particularly good results are obtained when using the drugs according to the described embodiments.

The contents of the antibody-containing protein of egg yolk can be sterilized to appropriately lower the concentration of pathogenic microorganisms without substantial loss of antibody activity in the result. Analysis of the antibody spectrum, for example ELISA or neutrality test, will distinguish this starting material from the yolk yolk food for preparing the preparations prepared for administration (preparation used according to the invention). Can be.

The starting material (an egg derived antibody) can be subjected to conventional concentration processes such as, for example, a general degreasing process with various solvents such as hexane, ethanol, acetone or carbon dioxide, or to further processes by:

And hydroxypropyl methyl cellulose (Yokoyama H. et al., A 2-step procedure for purification of chicken egg-yolk immunoglobulin-G-utilization of hydroxypropylmethylcellulose phthalate and synthetic affinity ligand gel, 1993, Poultry Science, 72, pp. 275 -281.)

Polyethylene glycol, dextran Sulfate , xanthan (Akita EM, Nakai S., comparison of four purification methods for production of immunoglobulin from egg laid by chickens immunized with an enterotoxogenic E. coli strain, 1993, Journal of Immunological Methods, 160 (2), pp. 207- 214.)

Ethanol (Toshio Horikoshi, et al., IgG Antibody from Hen Egg Yolks: Purification by Ethanol, 1993, Fractionation Journal of Food Science 58 (4), 739-742.)

And ultrafiltration (Hernandez-Campos FJ et al, Purification of Egg Yolk Immunoglobulin Y (IgY) by Ultrafiltration:. Effect of pH, Ionic Strength, and Membrane Properties, Journal of Agricultural and Food Chemistry, 2009 Dec 8. [Epub ahead of print])

Lithium sulfate (Bizhanov G. et al., A novel method, based on lithium sulfate precipitation for purification of chicken Egg Yolk Immunoglobulin Y, applied to immunospecific antibodies against Sendai virus, 2004, Scandinavian Journal of Laboratory Animal Science, 31 (3), pp. 121-130.).

The mixture consequently contains additional co-factors which are the basis of the medicament used according to the invention in addition to the drug used according to the invention. Such cofactors may have a positive effect on the mechanism of action and / or tolerability of the medicament used according to the invention.

Particularly preferred uses according to the invention, preferably according to the preferred embodiments described above, comprise a daily dosage of 0.1-10.0 g, preferably 1.0-8.0 g, more preferably 2.0-7.0, of the preparation prepared for administration. It is characteristic to carry out treatment or prevention by g.

A very particularly preferred use according to the invention, preferably according to the preferred embodiments described above, is at least 1.5 wt.% Of the preparation, preferably the antibody and / or antibody fragment, prepared for administration, relative to the total weight of the preparation. At least 2.0 wt.%, More preferably at least 5.0 wt.%, And the daily dose of the preparation prepared for administration is 0.1-10.0 g, preferably 1.0-8.0 g, more preferably 2.0-7.0 g Or to carry out prophylaxis.

If a formulation containing a high concentration of antibody is used, it would be natural for a person skilled in the art to appropriately adjust the dosage of the formulation prepared for administration. In this case, the preferred daily dose is 0.1 g-5 g, more preferably 0.1 g-2 g. Enteric coating and / or encapsulation can further enhance the activity of the formulation. Combinations using higher concentrations of the formulation with enteric coating and / or encapsulation are possible.

A very particularly preferred use according to the invention, preferably according to the preferred embodiments described above, is 0.1-5 g, preferably of a daily dose of the preparation prepared for administration with enteric coating and / or enteric encapsulation. It is characterized by carrying out treatment or prophylaxis with 0.1-2 g.

Enteric coating or enteric encapsulation provides the advantage that the antibody contained in the preparation prepared for administration does not denature while passing through the stomach.

Preferred uses according to the invention, preferably according to the preferred embodiments described above, have an IgY antibody and / or IgY antibody fragment in an amount of at least 30%, preferably 60%, relative to the antibody content of the preparations prepared for administration. More preferably 90% and particularly preferably 100% and at least 1.5 wt.%, Preferably at least 2.0 wt.%, More preferably of the formulation of the antibody and / or antibody fragment prepared for administration relative to the total weight of the formulation Preferably at least 5.0 wt.%, Characterized in that the treatment or prophylaxis is carried out with a daily dose of a preparation prepared for administration of 0.1-10.0 g, preferably 1.0-8.0 g, more preferably 2.0-7.0 g. have.

Preferred uses according to the invention, preferably according to the preferred embodiments described above, are characterized in that the treatment or prophylaxis is carried out by administering a daily dose for 4-14 weeks, preferably 8-12 weeks. 12-week treatment is particularly preferred. In many patients, surprisingly good tolerability and particularly good therapeutic effects have been identified with respect to the above daily dose and duration of treatment.

Preferred uses according to the invention, preferably according to the preferred embodiments described above, are characterized by carrying out treatment or prophylaxis by long-term therapy.

Another embodiment according to the present invention

For the manufacture of a medicament for the treatment or prevention of a disease selected from group X,

a) a drug selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof, or

b) a preparation comprising a drug selected from the group consisting of an antibody, an antibody fragment, an insulin-like growth factor antagonist, a toll-like receptor antagonist,

In the case of asthma above, the drug does not include insulin-like growth factor antagonists and toll-like receptor antagonists,

1. The treatment or prophylaxis is performed orally and / or

2. The antibody and / or antibody fragment targets at least 5 wt.%, Preferably 10 wt.% Of Gram negative bacteria relative to the total antibody content of the drug.

Another embodiment according to the present invention

- Multiple neuropathy, single neuropathy, autonomic neuropathy, three fiber neuropathy, in particular autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E, F, G, H, The above symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis

-Adjunctival disease in collagenoses

-Lateral epicondylitis

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche syndrome (arthrosis of the clavicle joint)

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

Cardiovascular Disease

Irritable bowel syndrome

-Reactive arthritis

-Ulcerative colitis

Crohn's disease

Antibodies, antibodies for promoting apoptosis of mononuclear cells swallowing lipopolysaccharide, in the treatment or prevention of diseases anatomically pathologically correlated with diseases selected from the X and Y groups consisting of graft-versus-host disease Fragments, insulin-like growth factor antagonists, toll-like receptor antagonists, and mixtures thereof.

Preferred formulations prepared for administration for the use according to the invention

a) n specific antibodies each have an antibody content of at least 6 / n wt.% relative to the total antibody content of the antibody product,

b) two, three or more of the n specific antibodies target lipopolysaccharide-expressing microorganisms and

c) an antibody product comprising n specific antibodies, wherein the total content of n specific antibodies relative to the total antibody content of the antibody product is 7 wt.%.

Lipopolysaccharides are compounds of the fat-like (lipo-) component and the sugar component (polysaccharide). Lipopolysaccharides are contained, for example, in the outer membrane of Gram-negative bacteria and act as antigens. During the degradation of the bacteria, some of the lipopolysaccharide is released and poisons. This is called endotoxin.

Accurate information of particularly preferred formulations prepared for administration can be found in German patent application DE 10 2011 006 781.7 which describes more preferred examples.

Compared to the drugs thus far, particularly preferred formulations prepared for administration, including antibodies against endotoxins (eg, cow colostrum), have better tolerability.

The present invention

Multiple neuropathy, mononeuropathy (possibly without central trigeminal neuralgia), autonomic neuropathy, fibrofibropathy, especially autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C , D, E, F, G, H, the above-mentioned symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis; In particular, activated arthrosis, primary arthrosis, secondary arthrosis

-Adjunctival disease in collagenoses

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche Syndrome

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

Antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof, used for the treatment or prevention of diseases anatomically pathologically correlated with diseases selected from the group consisting of cardiovascular diseases. Drug A selected from the group consisting of

In the case of asthma, the drug A does not include an insulin-like growth factor antagonist and a toll-like receptor antagonist,

1. The treatment or prophylaxis is performed orally and / or

2. The antibody and / or antibody fragment discloses a drug which targets at least 5 wt.%, Preferably 10 wt.% Of Gram negative bacteria relative to the total antibody content of the drug.

Particularly preferred drug A according to the invention, preferably according to the preferred embodiments described above, is characterized in that the treatment or prevention is carried out orally.

More preferred Drug A according to the invention, preferably according to the preferred embodiments described above, is characterized in that the antibodies and / or antibody fragments at least partially target Gram negative bacteria.

In Preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist is at least partially monoclonal antibody, polyclonal Raw antibodies, primatized monoclonal antibodies, antibody fusion proteins, antibody fragments, conjugated antibodies, radiolabeled antibodies, bispecific antibodies and / or monoclonal intrabodies ) In the form of an antibody.

In Preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the monoclonal antibody is characterized in that it is selected from the group consisting of murine, chimeric, humanized and human monoclonal antibodies.

In a more preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the drug comprises immunoglobulin A, immunoglobulin D, immunoglobulin E, immunoglobulin M, immunoglobulin G and / or immunoglobulin Y It is characterized by including.

In more preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist are at least partially, preferably completely from algae It is characterized by the obtained.

In more preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist is at least partially, preferably completely from chicken. It is characterized by the obtained.

In Preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist are at least partially from liquid and / or dry egg yolk It is characterized by the obtained.

In very particularly preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist is at least partially solid egg yolk powder, preferably It is characterized in that it is obtained from dry degreasing egg yolk powder.

In a very particularly preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the drug is characterized in that it is a component of the medicament or a preparation prepared for administration and / or a component of the medicament.

In very particularly preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the daily dose of the preparation prepared for administration is 0.1 to 10.0 g, preferably 1.0 to 8.0 g, more preferably 2.0 It is characterized by carrying out treatment or prevention at 7.0 g.

In very particularly preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the antibody and / or antibody fragment, relative to the total weight of the preparation, comprises at least 1.5 wt.% Of the preparation prepared for administration, preferably Is at least 2.0 wt.%, More preferably at least 5.0 wt.%, And the daily dose of the preparation prepared for administration is 0.1-10.0 g, preferably 1.0-8.0 g, more preferably 2.0-7.0 g Characterized in that the treatment or prevention is carried out.

In extremely preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the content of IgY antibodies and / or IgY antibody fragments relative to the antibody content of the preparations prepared for administration is at least 7% and the total of the preparations The antibody and / or antibody fragment by weight is at least 1.5 wt.%, Preferably at least 2.0 wt.%, More preferably at least 5.0 wt.% Of the preparation prepared for administration, and the daily dose of the preparation prepared for administration is The treatment or prevention is carried out at 0.1-10.0 g, preferably 1.0-8.0 g, more preferably 2.0-7.0 g.

In preferred Drug A according to the invention, preferably according to the preferred embodiments described above, the treatment or prevention is carried out by administering a daily dose for 4 weeks, preferably 8 weeks, particularly preferably 12 weeks. It features.

In preferred Drug A according to the invention, preferably according to the preferred embodiments described above, treatment or prophylaxis is carried out by long-term therapy.

The present invention

For the manufacture of a medicament for the treatment or prevention of a disease selected from group X,

a) Drug A selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof, or

b) a medicament comprising a drug A selected from the group consisting of an antibody, an antibody fragment, an insulin-like growth factor antagonist, a toll-like receptor antagonist,

In the case of asthma above, the drug does not include insulin-like growth factor antagonists and toll-like receptor antagonists,

1. The treatment or prophylaxis is performed orally and / or

2. The antibody and / or antibody fragment discloses targeting at least 5 wt.%, Preferably 10 wt.% Of Gram negative bacteria relative to the total antibody content of the drug.

All the advantages and embodiments disclosed in connection with the use according to the invention are applicable mutatis mutandis for use in the treatment or prophylaxis of diseases selected from the group of drugs A or X according to the invention.

The present invention

- Multiple neuropathy, single neuropathy, autonomic neuropathy, three fiber neuropathy, in particular autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E, F, G, H, The above symptoms in multicellular group gamma globulin disease and / or renal dysfunction

-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))

Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis

-Adjunctival disease in collagenoses

-Lateral epicondylitis

Achilles tendon pain

-Calcaneal pain and heel spur

Brachial scapular periarthritis

-Tyche syndrome (arthrosis of the clavicle joint)

Arthropathy of the sacroiliac joint

-Muscular arthrosis of the chewing organs, head jawbone dysfunction

Cervical spine syndrome after slowing trauma

Diverticulitis in colonic diverticulosis

Neurodermatitis

- asthma

-Interstitial cystitis (pain bladder syndrome)

-Food allergies

Allergies to light, especially polymorphic skin diseases

Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy

-Mucosal ulcers in Behcet's syndrome

-Mucosal erosion in the plain cloth window

-Mucosal lesions in scleroderma

-Mucosal lesions in Sjogren's syndrome

-Migraines without symptoms

Cardiovascular Disease

Irritable bowel syndrome

-Reactive arthritis

-Ulcerative colitis

Crohn's disease

Antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like, for promoting apoptosis of mononuclear cells that swallow lipopolysaccharide, in the treatment or prevention of diseases selected from the X and Y groups consisting of graft-versus-host disease. Drug A selected from the group consisting of receptor antagonists and mixtures thereof is disclosed.

All the advantages and embodiments disclosed in connection with the use according to the invention are applicable mutatis mutandis to drug A according to the invention for use in the treatment or prevention of diseases selected from the group Y.

The present invention is described in more detail through the following examples, but the present invention is not limited to the following examples.

Unless stated otherwise, all (quantitative) data are by weight.

Example :

Manufacturing example  One:

Detailed information on the preparation of the preparations can be found in German patent application DE 10 2011 006 781.7 or PCT / EP2012 / 055456, both of which are incorporated herein by reference. Materials obtained according to the above information (dry, degreasing egg yolk powder) are used in the following examples. Agents include specific antibodies against the following antigens:

CA-GTase of Streptococcus mutans serotype c from MT8148 cells

- Seriously Payne (gingipain) (ATCC 33277) from the membrane of the blood Fort Monastir seriously balises (Poryphyromonas gingivalis)

Candida albicans cells (JCM 1542)

Escherichia coli F18 cells, serotype F107 (107/86)

Alpha- and beta-toxin from Clostridium perfringens type C (NCTC3227)

 Antigen of Salmonella typhimurium cells according to H. Yokoyama et al. (ATCC-13311).

The medicament included a total antibody content of about 2 wt.% Relative to the total weight of the medicament. The total antibody content included specific antibodies for the antigen type (listed above) of about 10 wt.% Relative to the total antibody content of the medicament. Each specific antibody type (targeting one of the above antigen types) in the medicament was present at about 10/6 wt.% Relative to the total antibody content of the medicament.

Manufacturing example  2:

Preparation Example 2 was prepared similarly to Preparation Example 1, except that the following antigens were used for immunization:

E. coli F18 cells, serotype F107 (107/86),

Alpha- and beta-toxin from Clostridium perfringens type C (NCTC3227),

Antigen of Salmonella typhimurium cells according to H. Yokoyama et al. (ATCC-13311).

Preparation Example 2 was also used in formulations such as effervescent powders and tablets (especially enteric tablets). The amount of Preparation Example 2 used was 0.375 g per tablet or 5 g per foam pack unit pack.

At this point it should be again emphasized that the determining factor for the use and activity of the resultant according to the invention is the content of specific antibodies (polyclonal or monoclonal). Since the medicament used in the following example is a product obtained from a natural source (chicken egg), there may be a change in ingredients, which is inevitable.

Example :

Neutralization power of IgY (production example 2)

Heparin was treated to extract blood from healthy volunteers and prevent the blood from clotting. Heparin blood was obtained. Heparin blood was separated into its components to obtain plasma. 2 ml of the plasma thus obtained were incubated with 2 ml of E. coli control standard endotoxin (50 EU / ml) at 37 ° C. and 5% CO ₂ for 24 hours. A basic plasma solution was formed that contained a defined amount of standard endotoxin. Additional references for the standard endotoxins used can be found in Limulus Amoebocyte Lysate, Endosafe Endochrome-K Test System (US License no. 1197).

Provision of test solution:

Test solution B: Test solution according to the invention for E. coli , Salmonella and C. perfringens (preparation example 2)

100 μl of the basic plasma solution prepared in step a) was removed, and b) was uniformly mixed with 100 μl of the test substance dissolved (from Preparation Example 2, IgY; 0.25 g / ml) dissolved in water. The dissolved test substance comprised a mixture of antibodies according to the invention against E. coli , Salmonella and C. perfringens (Preparation Example 2). In the next step c), at 37 ° C. and 5% CO ₂ , the solution was incubated for an additional 3 hours. Next, in step d), consider adding a LAL reagent later, add water to the solution, dilute to endotoxin concentration 2 EU / ml, and e) step 75, at 75 ° C. for 5 minutes, in a water bath. ) Was incubated (inactive).

The inert test solution was then tested by the LAL test (Endosafe Endochrome-K Test System). In consideration of the method provided by the manufacturer, the inert test solution was mixed with LAL reagent and the mixture was pipetted into a 96-well plate. Tests were performed and evaluated by ELISA readers.

Test Solution A: Comparative Solution without Antibody (Control)

Test Solution A was prepared similarly to Test Solution B, except for the difference that 200 μl of the basic plasma solution was removed in step a) and not performing step b).

Test solution C: Comparative solution without the antibody according to the invention (IgG, Lactobin N; Dr. Wolz Zell GmbH)

Test solution C was prepared similarly to test solution B, except that 100 μl of the lactobin 9 Lactobin) N solution (manufacturer: Dr. Wolz Zell GmbH) was used in step b). Antibody concentrations were consistent with in Test Solution B.

9 shows the ELISA test results of test solutions A, B and C. FIG. The test quantified the amount of free endotoxin in a particular test solution.

Test Solution A (Control Solution), which contained no antibodies for neutralization of endotoxin, had the highest free endotoxin amount.

In contrast, test solution B according to the invention had the lowest free endotoxin amount.

Compared with test solution C (comparative solution of lactobin N), test solution B according to the present invention showed significantly better neutralizing effect than lactobin N.

Examples :

Case 1:

Patient information: 32 years old, female

Pain Syndrome Duration: 9 Years

Diagnosis:

Complex site pain syndrome after combined injury of the right thumb with proximal and ankle fractures and nerve injury (CRPS type II)

After three surgeries (bone surgery, metal removal, correction of modified extensor tendons), duration of pain at rest and increased pain during and after exercise (pain posttraumatic mononeuropathy).

Local findings ( Local  Findings:

Hot and stinging feeling throughout the thumb area, more pain in the scar area, spontaneous blunt pain and pain caused by gentle contact (allodynia), and associated pain when pressure is applied (Hoffmann- to damaged skin nerves) Tinel signs). In addition, there was a constant rhythm and puncture pain (deep pain) in the two proximal joints of the thumb. Radiographic evidence of arthrosis (pain persistence of activated arthrosis) was observed in both joints. Compared with the left thumb, the right thumb was quite narrow. That is, the skin and soft tissue of the thumb were thin (atrophy).

Therapeutic reactions of pain:

There was no relief of pain from central and peripheral analgesics, antidepressants, anticonvulsants, and percutaneous electrical nerve stimulation.

Opiate administration of the sympathetic nervous system (GLOA) to the cervical sympathetic nerve stem completely eliminated all pain for an average of 48 hours.

Of immunized chicken Yolk  Derived endotoxin ( LPS Oral hyperimmunoglobulins for LPS hyper-IgY)  Evidence of Significant Disease Symptom Improvement:

Patients were recruited for treatment studies of anti-LPS hyper-IgY. The four-week study period was divided into two equal periods of 14 days each and administered different doses to provide a wide range of clinical effects (journal documentation of parameters on pain and quality of life) and immunological experimental parameters before and at the end of dosing. The impact on the was tested.

Treatment effect:

In the first two weeks of the study, daily intake of medication 2 × 1.25 g (2.5 g daily), including continued elimination of pulsating, pounding pain near the arthritic pain joint structure; At this dose Neuropathic surface pain did not change.

In the second period of the study, two weeks during, drug 2 x 2.5 g daily intake (daily dose 5 g) (Fig. 1) as a result neuropathic pain component (component) were significantly improved. Daytime fatigue (chronic fatigue) with concentration, range of activity (activity), symptomatic day, with freedom from pain and most significant recovery of hand function fatigue syndrome, physical exhaustion (exhaustion), sleep quality and mood were improved (FIG. 2).

In the experimental part of the study, in peripheral blood (reduction through apoptosis) There was a significant decrease in endotoxin-active monocytes, a decrease in the total number of monocytes relative to normal levels, 22 Quantitative analysis of immune-transmitters (chemokines, cytokines, growth factors) is variable In general, the plasma concentrations of inflammatory proteins were decreased and most of the anti-inflammatory protein factors showed a significant increase.

Withdrawal attempts:

At the end of the study, trial administration continued because of the lack of alternatives. After 4-5 days, pain and general symptoms returned and IgY was discontinued twice.

summary:

Neuropathic pain in the damaged peripheral nerve area has already existed as an independent diagnosis of known etiology and pathogenesis and these characteristics have been distinguished from such pain from idiopathic pain syndrome. Some medications are approved for the treatment of mono- and polyneuropathic pain and there is an evidence-based treatment recommendation that includes non-drug ingredients. However, significant discrepancies between the quality of treatment effect and the degree of side effects and complications indicate a significant gap affecting both patient care and scientific evidence.

Surprisingly, the positive effects of certain IgY drugs in female patients indicate that in each patient, even in injury-induced mononeuropathy, blood cell-mediated endotoxins may play a role in the chronicization of pain. .

1 is a graphical representation of pain levels as an average of daily changes in values over the two study periods.

The vertical axis shows the numerical rating scale (NRS). The vertical axis has a value ranging from 0 to 10, where "0" means no pain and "10" means the best pain imaginable. The horizontal axis shows time in days.

According to the visual analogue scale (VAS), NRS is the most common way to measure acute and chronic pain based on pain diary to produce meaningful results on treatment effects. Patients with chronic pain are familiar with this method of measuring the intensity of their pain.

Patients began recording journals at the start of the trial treatment on day 15.

Instead of daily figures, the mean values for both periods are shown.

2 is a graphical representation of the quality of life parameters (physical exhaustion, concentration, mood, activity, sleep quality, bowel movement).

The positive effect on the quality of life parameters is particularly clearly shown by reduced daytime fatigue and increased range of activity (activity). A scoring rating scale, where 0 = no disease symptoms and 10 = peak of disease symptoms, is used similarly to measurement of pain. Patients with chronic pain are familiar with this format for measuring the intensity of their pain by recording pain logs.

Case 2:

Patient Information: 39 years old, female

Complex site pain syndrome duration: 30 years of soft tissue rheumatism, 20 years of arthrosis, 5 years of neuropathy following nerve injury

Diagnosis:

1. soft-biological rheumatism

2. Severe arthrosis with pain in the right knee joint during rest and exercise. Condition after bilateral hip arthroplasty (arthrosis).

3. Painful mononeuropathy with stiffness after irreversible nerve injury.

Local findings ( Local Findings ):

Severe swelling and high fever in the right knee joint with pain during unbearable night rest, despite cooling with ice packs and taking anti-inflammatory agents.

Pasty swelling, right spastic equinus with superficial burning sensation and shooting neuralgia. Tender musculature, tendon attachments and tenderness in the soft tissues of most joints.

Therapeutic reactions of pain:

Despite the long-term treatment and use of walking aids of antidepressants, anticonvulsants and antirheumatic agents, the most important daily functions have been severely limited, mainly by pain.

Of immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  High ( hyper ) - IgY ) Evidence of significant improvement in disease symptoms of oral therapy:

Patients in Case 1 participated in the same study.

After 6 days of treatment with an initial dose of 2 x 1.25 g of IgY, soft-tissue rheumatism had already been alleviated and there was an improvement in the overall quality of some life parameters (see Figure 4). In the last five days of the study, the double daily dose (5.0 g total) again resulted in a significant improvement in all pain symptoms, which was unexpectedly very evident in pain in the left foot neuralgia and rest in the right knee joint. There was a decrease in swelling and high fever, even when no anti-inflammatory agent was taken (FIG. 3).

 There was a significant decrease in endotoxin-active monocytes in peripheral blood (reduction through apoptosis), a decrease in the total number of mononuclear cells to normal levels and quantitative analysis of 22 immune-transmitters (chemokines, cytokines, growth factors) It showed a steady decrease in plasma concentrations of protein and a significant increase in anti-inflammatory central protein factors.

Withdrawal attempts:

Treatment with study medication continued because no positive results could be obtained by other known alternatives. Efficacy was regulated and confirmed by two withdrawal attempts conducted over a year.

summary:

Surprisingly, oral IgY treatment was effective for neuropathic pain associated with mononeuropathy following peripheral nerve injury.

In addition, for pain, the swelling and clinical inflammatory signals of activated arthrosis in the knee joint have improved subjectively and objectively.

Activated arthrosis is an independent diagnosis with very clear etiology and pathogenesis as well as objective radiological and clinical diagnostic criteria.

This case provides evidence that there is a causal relationship between the endotoxin load of immune cells circulating peripheral blood by orally administered antibodies and the endothelial load of blood cells and the inflammatory activation of arthrosis in the knee joint. To provide.

This causal relationship, at least to endotoxins, has never been investigated and therefore has not been proven and therefore cannot be expected.

3 is a graphical representation of the pain levels of the three pain phenotype by means of a sliding three-day average. Pain levels are determined by patient use of the NRS method. Each measurement point is the average over the previous three days (“sliding three-day average”).

3 shows the treatment of anti-LPS high-IgY

Of soft-tissue rheumatic pain (muscle, limb and tendon pain)

Activation of unspecified left knee arthrosis pain (joint pain; mainly arthrosis left knee)

Showing triggers of synchronous reaction of neuropathic pain after peripheral nerve injury (right common iliac nerve; neuralgia (peroneal lesion)).

4 shows the 3-day average change,

A graphical representation of the vaginal course of life parameters (physical exhaustion, concentration, mood, activity, sleep quality, bowel movements) for the patient during the trial treatment.

4 shows treatment with anti-LPS high-IgY.

Daytime fatigue (body exhaustion)

ㆍ intensive

ㆍ Activity Range (Activity)

ㆍ Show the result of improvement in mental health (mood).

The severity of disease symptoms is expressed by the NRS on the longitudinal axis. The measuring point on the longitudinal axis is the mean value of the NRS ratings from the patient log for the previous three days.

Case 3:

Patient information: 56 years old, female

Duration of complex site pain syndrome: 13 years

Diagnosis:

1. Complex site pain syndrome in both upper extremities

2. Bilateral perceptual thigh neuralgia = compression syndrome of the outer thigh skin nerve, a nerve pathway under the inguinal ligament.

3. Morton's metatarsalgia (compression syndrome of the plantar nerve between the first and second toes) on both feet

4. Irritable bowel syndrome with severe burst (colic) of abdominal pain mostly concentrated in the lower abdomen

5. Painful bladder syndrome / interstitial cystitis (PBS / IC), bladder disease of unknown etiology. Even when the organ contains very small amounts of urine, there is constant pain in the bladder, accompanied by a strong urge to urinate. You may also have very severe pain in urination. There is no evidence of urinary tract infection or other local pathology. Endoscopic examination of the bladder mucosa showed signs of inflammation. Biopsies usually show an increase in eosinophilic granulocytes and mast inflammatory cells suggesting allergic inflammation.

6. Neurodermatitis

case history  And Local Findings :

After a minor accident, the patient developed a left hand complex pain syndrome (CPRS) that spreads throughout the left upper limb (shoulder-arm-hand syndrome). This is a combination of three diagnoses: periarthritis of the shoulder joint, epicondylitis humeri radialis, and CRPS of the hand. The patient also had nerve compression syndrome in the bony groove of the elbow borescope accompanied by sensory and motor neuron loss in the affected hand.

As the disease progressed, the patient also developed a compression syndrome (carpal tunnel syndrome) in the right metacarpal nerve. After surgical treatment for this, complex area pain syndrome also developed in the right hand in addition to pain, and the patient suffered a complete loss of function of both hands.

Therapeutic reactions of pain:

During the unsuccessful day-to-day multidisciplinary pain treatment of the course of June, the patient developed different compression syndromes of the peripheral nerves of both thighs and feet (aberrant perceptual neuralgia and Morton neuroma).

The full clinical picture, including neurodermatitis, was eventually successfully treated with intravenous injection of the human C1 esterase inhibitor (C1-INH) Berinert® in combination with low-molecular weight heparin. Since the patient did not have a C1-INH deficiency, this was an off-label treatment (treatment for unapproved indications). Treatment had to be continued at an average of 8 weeks.

Of immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Evidence of equivalent elimination of disease symptoms of high-IgY) oral therapy:

When the effects of the most recent Berinert ® injection subsided and all of the above symptom symptoms returned as well as neurodermatitis and severe headache, the patient only accepted the IgY treatment study described in Examples 1 and 2.

Treatment effect:

In the first week of the study, an initial dose of 2 x 1.25 g of IgY completely eliminated headache and abdominal pain. In the second study phase (beginning of the third week of IgY treatment), neuropathic pain and sensory disturbances in the lower and upper arms and shoulder pain and limited exercise due to nerve compression symptoms have already disappeared (FIG. 5). At the end of the study, daytime fatigue continued to a low degree, but common disease symptoms and neurodermatitis of the combined health problem disappeared with pain. After continuing treatment at a low initial dose, fatigue symptoms disappeared the next month.

In the experimental part of the study, there was a significant decrease in endotoxin-activated mononuclear cells in peripheral blood (reduction through apoptosis), a decrease in the total number of mononuclear cells to normal levels and 22 immune-transmitters (chemokines, cytokines, growth). Quantitative analysis of the factors) showed significant and successful changes by treatment for all study participants. Among the patients, however, the biggest change was in different spectra of chemokines.

Withdrawal attempts:

Following the study, study treatment at lower doses continued for 4 months. Symptoms returned only when study treatment was discontinued for more than three months.

summary:

There was a surprising effect on neuropathic pain, and neuropathic dysfunction is most often caused by generalized compression syndrome of peripheral nerves, not peripheral nerve damage. This effect occurred within a week at the lowest dose and was qualitatively equivalent to the Berinert® treatment.

After 15-16 days, the pain and dysfunction of the shoulder and forearm joints caused by abnormal acute periarthritis and epicondylitis were completely eliminated. This very common form of inflammatory periarticular disease is actually associated with the patient's mysterious systemic disease, but surprisingly the extremely successful response to IgY treatment suggests that the general nature of the disease is a form of endotoxin-mediated disease of the motor system. . Thus, antibody drug therapies, particularly with IgY specific agents, are likely to be promising when used at an unknown rate in patients with these diseases.

By this analogy, the same can be estimated for the symptoms of irritable bowel symptoms and interstitial cystitis.

No clear neurodermatitis returned to the patient during IgY therapy. Irritable bowel syndrome, interstitial cystitis and neurodermatitis have common immunological characteristics: pathologically activated mast cells are associated with changes in proven inflammatory organs. This cell type of the immune system also has a binding site for endotoxins so that in certain circumstances these cells can also be activated simultaneously in various organ systems by these toxins. In certain oral antibody therapies with IgY, endotoxin is already partially removed from the intestine.

5 shows the change in intensity of pain symptoms (three most severe pain phenotypes) of this patient through self-assessment using NRS levels after initiation of treatment with certain IgY agents. The measuring point on the longitudinal axis is the mean value of the NRS ratings from the patient log for the previous three days. The horizontal axis shows time in days. The patient began taking IgY on day 15 and the dose was twice that of 29 days.

Case 4:

Patient information: 55 years old, female

Duration of complex site pain syndrome: 12 years

Diagnosis:

Neuralgia of the 1st and 3rd right trigeminal sections after shingles (trigeminal mononeuropathy after shingles)

2. Migraine without symptoms

3. Both Achilles tendon pains with signs of autoimmune disease (undifferentiated collagen) (Inflammatory Attachment Disease of Achilles tendon)

4. Irritable Bowel Syndrome with Temporary Diarrhea

5. Secondary Antibody Deficiency Syndrome (IgG and IgA)

6. Evidence of Chemical Experiments of Autoimmune Diseases (Autoantibodies) Associated with Undifferentiated Glioma

case history  And Local Findings :

Long ago (> 10 years), the patient had herpes zoster (shingles) at the forehead and maxillary points of the right trigeminal nerve, had a viral infection removed once, especially behind the right eye, around the right end of the nose and tongue The episodes of chronic pain, numbness and acute pain have persisted.

Facial pain attacks continued daily before or after an episode of diarrhea characterized by rapid diarrhea (irritable bowel syndrome).

Facial pain attacks also always involved increased sweating and / or tremors.

Until onset of IgY therapy, there were no migraine headaches prior to facial neuralgia for an average of seven days each month.

In later stages of the disease, the patient began to suffer from both Achilles tendon pains, which gradually caused severe mobility problems. Achilles tendon pain is, for example, an achilles tendon pain as an independent inflammatory disease after tendon tension, or as a secondary symptom of rheumatic disease.

Therapeutic reactions of pain:

Long-term treatment to control pain consisting of a combination of six different drugs: antiepileptic (pregabalin; pregabalin), two antidepressants (amitriptyline; amitriptyline and duloxetine), analgesic flupirtine And opiates tilidine and fentanyl (200 μg stick as needed). The patient has already consulted in 9 pain practices, neurology clinic and orthopedic (for Achilles tendon pain). She suffered without relief from all three pain syndromes as well as irritable bowel syndrome in addition to the side effects of many treatments.

Hyperimmunoglobulin (Anti-LPS High) on Egg Yolk-Derived Endotoxin (LPS) in Immunized Chickens hyper ) - IgY Evidence of significant relief in disease symptoms of oral therapy:

Specific IgY treatment was started at the lowest test dose (2 × 1.25 g). Another migraine headache occurred, so treatment did not start as single. Achilles tendon pain and irritable bowel symptoms also disappeared within a month.

Post shingles neuralgia did not change at this dose as medical use. After 3 months of treatment at the lower test dose, by doubling the dose (2 × 2.5 g), the number of facial pain attacks was much less and the duration of the attack was shortened from one hour to just a few minutes. The intensity of pain remained unchanged. Other medications reduced the dose, while some medications were omitted entirely. The general welfare of the patient has been fundamentally improved.

The numbness of the facial skin and tongue persisted, but all remaining pain and disease symptoms disappeared completely by replacing the antibody deficiency (relatively less) by intravenous administration of human immunoglobulin.

summary:

Shingles-Post Neuralgia

Post shingles neuralgia is an independent clinical diagnosis of a known etiology. It is a mononeuropathy consisting of permanent nerve damage after viral infection. Science does not provide a satisfactory interpretation of the reason why untreated herpes zoster neuralgia develops in the rest of the patient's life after infection is cured, in only a few patients. Binding of endotoxins to nerve roots damaged by infection may be one of several mechanisms that are part of the constant pain. This case study strongly supports this hypothesis: During treatment with certain IgY medications, the patient's migraine, irritable bowel syndrome and Achilles tendon inflammatory changes disappeared. This significant effect can only be understood in terms of the neutralizing effect of IgY on the movement of endotoxin in vivo. Significant reductions in the duration of the facial pain episodes and a decrease in the number suggest that such induction mechanisms are at least associated with this pain syndrome.

Achilles tendon pain

The complete elimination of pain and inflammation in the Achilles tendon in the context of autoimmune disease is surprising, especially since the previous patient had no relief or therapeutic effect. Inflammatory adherent disease (a generic term for all inflammatory diseases of tendon and tendon attachment) is often known to be resistant to treatment.

migraine

The patient's migraine headaches could not be adequately treated with certain migraine drugs and pharmacologic seizure preventives (β-blockers) taken by the patient while the attack was ineffective, allowing the patient to continue their daily work in the presence of migraine headaches. . This resulted in the absence of an average of seven days each month due to migraine headaches. This case plays a role in this disease and clearly shows that endotoxin migration is the only and completely surprising part.

Case 5:

Patient Information: 65 years old, male, study number 17

Duration of pain syndrome: 35 years of headache, 1 year of neuropathy of the right labial nerve, 3 years of right epicondylitis.

Diagnosis :

1. Endless symmetrical tension-type headaches after severe episodes of "Tick-mediated encephalitis (TBE)" 1974 (brain and meningitis caused by viral transmission by tick bites)

2. The brachial radial and right ulnar epicondylitis with significant dysfunction of the entire right arm and pain at severe rest.

3. Lumbar back pain radiated throughout the right right nerve, the residual effect of surgical operation of the herniated disc herniation one year ago (monopathy of the nerve after compression injury).

Local findings ( Local  Findings:

Very soft periosteum around the muscle attachment of the right lower arm muscle of the upper arm at the elbow area. Radiation pain during normal exercise with tension in muscle attachment (lifting with screws, lifting objects with outstretched arms, such as hanging a coat on a door hook, for example).

No pulsating pain in the lumbar spine, buttock pain (passive signs of Laseque) when passively lifting the right leg in an extended position while lying, no achilles tendon and right patellar tendon reflex, no motor weakness of the right leg .

Therapeutic reactions of pain:

 After several years of meningitis treatment with severe side effects (liver damage), the patient no longer received any treatment for his pain. As part of the patient rehabilitation program, physical therapy (after meningitis and disc surgery) has not been successful.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Evidence of significant improvement in disease symptoms, in some cases completely eliminated, with oral therapy of high-IgY):

During the study there were all three pain phenotypes, significant changes in pain levels recorded before continuing the study, and improvements that began to decrease in mean values during the low-dose state (2 x 1.25 g per day), and this effect was associated with high dose ( More clearly at 2 x 2.5 g per day). During follow-up, back and rump pain completely disappeared while the patient maintained a high dose. The patient no longer experienced any dysfunction because the pain and dysfunction caused by epicondylitis was greatly reduced and the pain was less under physical stress. During the follow-up, the headache appeared only early in the morning and no longer affected the patient (FIG. 6). In the graphical representation of the numerical plots recorded for assessing pain levels in the pain log, the patient's free-to-shoe rating was not reflected because the patient recorded the daily high, not the daily average. Did.

In the experimental part of the study, there was a relatively small decrease in endotoxin-activated mononuclear cells in peripheral blood (reduction through apoptosis), a slight decrease in the total number of mononuclear cells to normal levels and 22 immune-transmitters (chemokines, cytokines). Quantitative analysis of Cain, Growth Factor), compared to other study participants, together with the highest level of anti-inflammatory protein factor (eg, Interleukin 4 and 5) increase in inflammatory protein (eg, TNF-α IL- 6, IL-8) showed an unbalanced decrease in plasma concentrations.

Withdrawal attempts:

The patient finished taking IgY for 6 months until the headache and pain of epicondylitis began to affect quality of life again after 141 days. After that, he was treated only as needed for a 4-5 day period and was able to control the pain level as desired.

summary:

meningitis  After chronic headache, neuromuscular compression Ass  Mononeuropathy of nerves, Epicondylitis

The mononuclear cell-bound "endotoxin load" in the patient's blood is likely to be related to the etiology of the 3 chronic pain phenotypes that are usually diagnosed independently in medicine. Residual damage to the brain and meninges (TBE) and muscle nerves following muscle infections is a biological weakness that can endothelial-filled immune cells attach and maintain a local immune response (causes pain). An explanation of the cause for this epicondylitis is immune activation in the nerve supply of the right arm (and not the painful elbow).

FIG. 6 shows pain symptoms of three different classes of patients (patitis, headache and The change in intensity of back-bowel pain / monopathy) is described.

The measuring point on the vertical axis corresponds to the NRS reading measured daily (there is no 3-day average due to the relatively low fluctuations in pain level). The horizontal axis shows time in days. IgY treatment began at day 15 and continued with doubled doses from 29 to 42 days. Treatment was then continued at a low maintenance dose until 141 days.

Example 6:

Patient information: 65 years old, male

Duration of Pain Syndrome: 11 years, including 3.5 years postoperative discontinuation of symptoms (Jannetta procedure).

Diagnosis:

Central trigeminal neuralgia, II. And III. Right branch (diabetic mononeuropathy)

2. Type 1 diabetes with stable insulin pump, diabetic peripheral polyneuropathy, diabetic nephropathy (proteinuria, still functioning normally)

History and local findings Local Findings ):

Neuralgia was more than 10 years after the onset of diabetes and initially responded to carbamazepine, then to the addition of other anticonvulsants, and finally to microvascular decompression of the trigeminal neural muscle (MVD or synonym: Jannetta procedure). 3.5 years was painless. When the attack resumed, the dose of carbamazepine rapidly increased, with a pronounced side effect affecting the central nervous system with the risk of disability (professional driver, loss of driver's license).

Findings:

Tingling malaise in small portions of the oral mucosa of the upper lip and lower jaw cheeks. Strong avoidance of air flow or contact generation that may cause pain attacks in this area. A daily burst of consecutive repeated pains by the meal, but still tolerating toxic blood levels of antiepileptic drugs (apparently low levels of pain at the beginning of the study, FIG. 7). Personal problems and work-related stresses that increase the likelihood of an attack.

Peripheral leg polyneuropathy is purely sensory and consists of a feeling of walking in cotton wool and edema of the feet and lower legs.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Evidence of complete relief (removal) of central trigeminal neuralgia and improvement of symptoms of diabetic polyneuropathy with treatment of high-IgY):

Within the first 14 days of the study, at an IgY-dose of 2 x 1.25 g per day, the patient was already painless and the patient no longer suffered from side effects at 1,200 mg, while the attack began to recur Reduced to 900mg mg with effect. At a daily dose twice the IgY dose of 2 x 1.25 g, the patient was painless again and reduced the carbamazepine to a daily dose of 450 mg for the remainder of the study (FIG. 7). During IgY therapy, sensory symptoms completely disappeared in the skin and mucous membrane areas, which are the major sites of pain attack. For idiopathic central trigeminal neuralgia, there was no sensory impairment with the exception of therapeutic interventions that caused nerve damage. This case is therefore a diabetic mononeuropathy of the trigeminal nerve site rather than the idiopathic form of neuralgia.

During IgY therapy, the patient also regained feeling in both feet and significantly reduced the tendency for edema of the feet and lower legs. At the site of diabetic polyneuropathy, the patient was painless. The effect on the symptoms of polyneuropathy was surprising.

The patient was then able to completely stop taking the antiepileptic carbamazepine after 1 month while taking a daily dose of 5 g of IgY and remained asymptomatic with a 2.5 g IgY maintenance dose per day. . In repeated attempts to reduce the daily dose, sensory impairment has returned to the same place as the patient generally knows as a notice of pain attack.

In the experimental part of the study, the patient showed a significant decrease in endotoxin-activated mononuclear cells in peripheral blood (reduction through apoptosis), a decrease in total mononuclear cell count to normal levels. 22 Quantitative analysis of immune-transmitters (chemokine, cytokine, growth factor plasma concentrations) showed significant reduction and anti--reduction of growth factors IGF-1 and GMCSF and proinflammatory cytokines IL-8 and IL-7 in patients. Inflammatory cytokines IL-4, IL-5 and IL-13 were shown to increase.

Withdrawal attempts:

The patient was only able to reduce the dose of study treatment (5 g of IgY daily dose), but not without treatment. The specificity of the effect of the dominant set of antibodies on endotoxins was compared with the therapies associated with high-immunity IgY agents against antigens of periodontal disease pathogens.

summary:

Diabetic mononeuropathy of the trigeminal nerve

Continued elimination of idiopathic central trigeminal neuralgia symptoms through long-term treatment of cow colostrum-derived oral immunoglobulins is known, but in this case, no central trigeminal neuralgia based on diabetic mononeuropathy is known.

Diabetic Polyneuropathy

In this case, the simultaneous treatment effects on autonomic components and sensations (loss of sensation and lower leg edema) of polyneuropathy gave the first surprising indication of the effectiveness of the agent in diabetic polyneuropathy.

FIG. 7 illustrates the change in intensity of pain attack due to central trigeminal neuralgia by patient self-assessment using NRS scores during the study period.

 The vertical axis shows self-assessment of pain levels by daily NRS. The study day is shown on the horizontal axis. Treatment was started on day 15 and continued to 29 days in double dose. Prior to IgY therapy, pain was not controlled with a daily dose of 1,200 mg of carbamazepine, which was a toxic level in the blood. As IgY therapy commenced (from day 15), the carbamazepine dose decreased to 450 mg below the daily dose (42 days) at intervals until the end of the study. At the end of the study, the patient had no symptoms. Carbamazepine has since ceased entirely.

Case 7:

Patient information: 43 years old, female

Duration Of Bottle: 9 Years

Diagnosis:

1. the complex area pain syndrome of the right lower extremity

2. Idiopathic back pain

3. Exceptionally severe irritable bowel syndrome, complicated by daily uncontrolled bowel discharge during stomach cramps

4. Painful bladder syndrome / interstitial cystitis (PB / IC), also accompanied by bladder spasms and uncontrolled urination

History and local findings Local Findings ):

After the valgus valgus surgery of the right foot, five other attempts of surgical treatment were performed as a result of very severe neuropathic pain, which is rarely cured after surgery, which manifests as complex site pain syndrome that does not respond to medication.

Complex pain therapy of limited intensity improved pain in the feet.

Following unsuccessful attempts to treat inflammation and severe pain with medicine (long-term antibiotic therapy due to suspected chronic infection, anti-inflammatory long-term treatment), the irritable bowel symptoms present are completely out of control. . Intestinal pain was associated with watery stools that occur in bed at night in an uncontrolled manner. Painful bladder spasms have led to loss of sphincter control.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Field of High-IgY Kills bowel ) And evidence of significant relief (removal) of bladder disease symptoms:

Neuropathic pain symptoms in the right foot have already improved under previous combination therapies (psychological, physical- and drug therapy-related, partial combined-patient treatment) and only slightly improved during the treatment of study medication. The foot still could not bear any more load. Severe, back pain, especially in the neck and shoulder areas and the lumbar-sacral region, was permanently improved by 2 points on the scoring rating scale. Intestinal and bladder spasm completely disappeared at the end of the IgY study with a daily dose of 5 g of a specific IgY agent. The daily number of bowel movements dropped from an average of 9 (2-17) to 2 (Figure 8), and the stool formed no longer containing any undigested food ingredients. Uncontrolled bowel movements and urination completely stopped.

The result of the treatment was then maintained for 1 year with an IgY of 4 g daily dose.

In the experimental part of the study, the patient showed a significant decrease in endotoxin-activated mononuclear cells in the typical therapeutic response, in particular peripheral blood (reduction through apoptosis) and a decrease in the total mononuclear cell number to normal levels. 22 In quantitative analysis of immune-transmitters (chemokine, cytokine, growth factor plasma concentrations), growth factors IGF-1 and GMCSF and proinflammatory cytokines IFN-γ, TNFαR-1, IL-8 and IL- A significant reduction of 6 and an increase in the anti-inflammatory cytokines IL-4, IL-5 and IL-13 were produced.

Attempt to abort Withdrawal attempts ):

Several attempts have been made to end IgY-therapy, but the intestinal and bladder symptoms have returned a few days after each attempt.

summary:

Irritable bowel syndrome, Pain  Bladder syndrome / interstitial cystitis ( PBS / IC ), Also symptoms of autonomic neuropathy

Because this is a combination of comparable bladder symptoms, this type of irritable bowel syndrome is certainly rare. Nine years of failure to attempt to treat foot and extreme pain with medicinal therapies significantly impaired the barrier function of the intestinal mucosa and certainly promoted and contributed to the degree of disease abnormality. Prior to IgY treatment, over 90% of endotoxin-activated blood mononuclear cells (CD14 + and CD45 +) ultimately resulted in this barrier damage, accompanied by insufficient cell death of antigen-receiving mononuclear cells in the intestine. This barrier damage resulted in abnormally high endotoxin load throughout the body. In laboratory tests at the end of the study, endotoxin binding mononuclear cells (CD14 +) dropped to 65% and “activated” mononuclear cells (CD45 +) dropped to 10%. Simultaneous intestinal and bladder symptoms with significant dysfunction of the sphincter of both organs suggest that endotoxin is a major cause of autonomic neuropathy. Pain and dysfunction of the intestine and bladder can thus be interpreted as impairment of the autonomic nerve supply of both organ systems, largely under the influence of endotoxins.

FIG. 8 shows the action / effect of IgY agents on the three vaginas (quality of sleep, activity and bowel movements) of life parameters of this patient with severe signs of irritable bowel syndrome with diarrhea.

The vertical axis shows self-assessment scores and daily bowel movements for "quality of sleep" and "activity" using daily NRS values.

The horizontal axis shows time in days. Study treatment began at 15 days and continued at double dose from 29 to 42 days.

Case 8:

Patient information: 55 years old, male

Duration of illness: 19 years

Diagnosis:

1. Post-Lyme borreliosis syndrome with chronic encephalitis, a condition after Lyme heart infection

2. Multiple neuropathy

3. Irritable Bowel Syndrome with Diarrhea

4. Chronic Burnout / Fatigue Syndrome (CFS)

5. Polymorphic Skin Disease

History and local findings Local Findings ):

Chronic mobile erythema, then Borrelian radiculitis (Garin-Bujadoux-Bannwarth syndrome), encephalitis, and polyneuropathy. Severe intestinal symptoms caused by bacterial overgrowth as a result of oral and intravenous long-term antibiotic therapy. Full disorder due to pain and the formation of excessive CFS.

Afterwards: the development of polymorphic photodermal disease

Intermittent treatment of nerve pain (polyneuropathy) with polyvalent human immunoglobulin (IVIg). This therapy significantly regulated pain and CFS, and as a result significantly improved optical skin disease. After eradication of the above chronic Helicobacter pylori infection, optical skin disease was further improved (duration of improvement: 6 months).

After that, IVIg was no longer effective. The patient lived in a totally dark place with only artificial lighting without UV-B-. I lie down and do home care.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Hyper-IgY) treatment with polyneuropathy, Optical skin disease , CFS  And evidence of significant improvement in irritable bowel syndrome:

At Dermatological University Clinic Wurzburg Inpatient-patient treatment is approved.

Admitted to a completely sun-resistant single room. Start treatment with a specific IgY drug at a daily dose of 2 x 1.25 g, followed by gabapentin Pain therapy continued (polyneuropathy). As a result Significantly improving neuropathic pain Bowel movement Completely normalized. A week later, the dose of IgY drug was increased to 3 x 1.5 g per day. In this treatment , sun exposure was increased from 300 to 9,000 lux per day until discharged for home care after 4 weeks.

summary:

Neuroborelia  Multiple polyneuropathy, chronic exhaustion / fatigue syndrome ( CFS Irritable bowel syndrome, polymorphism Optical skin disease

During the six-year period, all disease symptoms were controlled by IVIg, and to the extent that the patient was unable to work, he was mostly self-sufficient. Even in the optimal conditions, ie in the first four weeks after intermittent treatment of 30 g of IVIg, the patient could not walk more than 500 m three times a day. Exercise limits were determined by increased pain, symptoms of burnout, and severe itchy inflammatory skin changes when the low light tolerance threshold was exceeded. The skin change, once it happened, took weeks to heal. The antiepileptic gabapentin provided minimal relief at least within narrow limits to itching. Antihistamines and cortisone did not relieve symptoms.

Polyneuropathy

Polyneuropathy is characterized by stinging pain when moving in the left hemisphere of the body, which is projected to the part of the body where sensitivity is reduced. In addition, there is symmetrical pain in secondary and tertiary branches, caused by biting or touching the skin (trigeminal neuropathy). During treatment with IgY, the symptoms of trigeminal neuropathy disappeared completely and other pains were greatly reduced, despite the very weak condition of the patient, getting up in bed, getting dressed, taking a shower, writing or walking short distances. Activities like this were possible without any pain.

CFS

Severe daytime fatigue through the disease, which was interrupted only periodically when the patient received IVIg treatment, was alleviated under IgY therapy, allowing the patient to attend most daily activities without requiring rest.

Irritable bowel syndrome

Irritable bowel syndrome consists of abdominal spasms and frequent excretion of unformed feces. In particular, the patient reported that he could never empty the rectum completely, and for half an hour or more after defecation, a small amount of semi-liquid state continued to come out without attention, so he had to wear a pad. Loss of control of bowel excretion was a clinical sign of autonomic neuropathy. These symptoms disappeared the first week of IgY treatment.

Polymorphism Optical skin disease

Polymorphic photodermatosis was very acute. Testing of small areas of the skin with defined doses of UV-B resulted in strong local reactions as a result of typical dermatological diseases.

In particular, the response to severe clinical condition of IVIg is described in the case report as a successful treatment by plasmapheresis (plasma exchange).

The substantial partial success of anti-endotoxin hyperimmune IgY treatment has been very surprising on the one hand and on the other hand provides evidence that endotoxin is involved as the etiology of this individual case.

Example 9:

Patient Information: 59 years old, male

Duration of illness: 6 months

Diagnosis:

1. Carcinoma, Surgery and Radiotherapy of the plantar surface (right)

2. Type 1 Diabetes

3. Neutropenia, anemia (results of radiation therapy)

4. Neuropathic Face Pain

5. Mucositis of irradiated oral mucosa

History and local findings Local Findings ):

In the lower right jaw / palp region, due to radiation therapy at the surgical site, the patient experienced an acute facial pain radiating from the lower jaw to the right ear caused by swallowing. Severe burning in the oral mucosa at the irradiation site.

With tramadol + metamizole, pain at rest was largely controlled. Due to pain, it is almost impossible to eat.

First treatment subcutaneously with 6.4 g of immunoglobulin. After several hours, neuropathic facial pain was alleviated, but local contact pain of oral mucositis was not alleviated.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  High-IgY) during treatment Mucositis  Significant improvement, evidence of unobstructed food intake:

Eating and drinking, immediate reaction of contact pain in inflamed oral mucosa. Normal food intake was restored most of the time.

summary:

Bacterial colonization of the oral mucosa may include endotoxin-forming bacterial populations. Since the sensory nerves at the end of the trigeminal nerve have binding sites for endotoxins (tol-like receptor 4), endotoxins can cause severe pain hypersensitivity in inflamed mucosal lesions. Binding of endotoxins by topically administered antibodies eliminates pain as well as inflammation caused by endotoxins. Unlike local anesthetic measures, antibodies also promote healing.

All the cases described above were performed with the antibody drug of Preparation Example 1. The therapeutic success of the use according to the invention is not necessarily limited to Preparation Example 1. Preparation Example 2 was used in the following example. Furthermore, better results can be obtained with alternative agents than with Preparations 1 and 2. One of ordinary skill in the art is naturally capable of optimizing the pharmaceutical composition in the context of the drug to be used or for the individual prescription or for the individual patient. It is therefore apparent to those skilled in the art that the use according to the invention is not limited to the preparations 1 and 2 used in the examples, and that the surprising effects of other drugs or agents to be used according to the invention are also expected.

Case 10:

Patient Information: 13 years old, male

Duration of disease: 6 months

Diagnosis:

1. Acute right brachial scapular periarthritis (rotary tendonitis)

History and local findings Local Findings ):

For about one week, the patient suffered from increased motor pain in the right shoulder joint. After 5 days, additional night rest pain developed, and after 6 days the right arm was not fully available. Flexing the elbow joint was so painful that it was impossible to dress alone and clench a fist (which causes shoulder pain).

The patient could not remember causing trauma or excessive strain. There is no history as of now, but only allergic asthma was present at the beginning of pain symptoms.

The right shoulder joint had severe pain with pressure in the entire rotator cuff area. In comparison with the other side, an increase in temperature in this part was also confirmed. A slight spread of soft tissue swelling around the shoulder joint into the upper shoulder bone area was also observed. The patient avoided any active movement of the arms and hands. Pain caused by all axes of motion limited the passive movement of the shoulder joint as much as possible.

This was typical of idiopathic acute periarthritis, which has not been treated until now.

Immunized chicken Yolk  Derived endotoxin ( LPS Hyperimmunoglobulin (anti- LPS  Under high-IgY) treatment Periarthritis Perfection  Proof of cure:

Therapy was carried out by administration of 2 × 1/2 bags of IgY effervescent powder (daily dose; corresponding to 2 × 2.5 g of antibody mixture). Painkillers were not prescribed or taken.

After starting therapy, the first follow-up consultation in the morning:

The patient slept again at night, dressed himself in the morning and tied the shoelace. Without significant pain in the shoulders, it was possible to greet and shake hands as well as spontaneously bend the elbow joint.

There was a continued improvement, with symptoms disappearing within 5 days. A total of 7 bags of IgY medication were taken. The last consultation with the patient was after 6 weeks. No recurrence of symptoms occurred.

summary:

Acute idiopathic periarthritis of the shoulder joint without prior treatment. IgY therapy led to rapid, unmarked treatment, which had already begun treatment at the first dose and was completely cured after 5 days.

Case 11:

Patient Information: 51 years old, male

Duration Of Bottle: 7 Years

Diagnosis:

1. Plain cloth window

History and local findings Local Findings ):

The disease existed for seven years. It is a rare autoimmune disease of the skin and mucous membranes. Signs at the oral mucosa site cause a wide range of mucosal losses, leaving behind severe painful ulcers (mucositis) that heal only under chemotherapy of the disease.

During this period, oral intake of food and beverages is barely possible.

Chemotherapy has yet to block older stages of disease. However, all attempts to progressively reduce chemotherapy have led to relapses, usually starting at the oral mucosa site.

Since the pain subsided a few hours after starting the dose, since the oral mucosa was treated with IgY, it was possible to maintain oral nutrition during the last two illnesses.

Over the past few days, the patient has noticed a small portion of the painful mucosal defect, again in the mouth, a sure sign that the disease recurrence begins again.

IgY Personal healing attempts by:

Topical symptomatic therapy with a dose of 2 x 1.25 g of IgY effervescent powder (IgY agent of Preparation Example 2) per day was performed until the first food intake was disturbed or possible without pain (up to a week).

Thereafter, treatment of enteric tablet form of IgY was started for the purpose of eliminating LPS as a possible trigger of systemic disease in the small intestine.

Dosage: 3 x 3 enteric tablets daily (corresponding to 3.4 g daily of IgY agent of Preparation 2) for a duration of one month.

During this period, oral therapy of IgY effervescent powder continued with minimal dose to keep the oral and pharyngeal mucosa intact.

 Material needed in the first month: 3 x 3 enteric tablets daily (approximately 3.4 g of the daily dose of the IgY agent of Preparation 2). 37 daily dosage units of 270 enteric tablets and effervescent powders are available.

At the end of each month, a decision was made to continue treatment at the same or changed dose. The effect of treatment was checked by the journal of disease symptoms, dose and course of immunosuppressive chemotherapy.

This is the first attempt of IgY therapy in a patient suffering from hernia. Treatment of mucositis (oral mucosa) in this patient has been successful in all past applications.

IgY Other course of the disease under treatment (status: 10.03.2012):

Under IgY effervescent powder dosing, after a painful mucosal lesion of the oral / pharyngeal cavity was alleviated, a significant improvement in general well-being occurred 4 days after the start of enteric tablets (3 × 3 tablets daily).

Complete elimination of chronic burnout symptoms

Reconstruction of physical ability

Removal of non-specific joint pain at the scapula site

In the next analysis of specific antibody titers (autoantibodies) in university hospital dermatology, the lowest titers were measured since the onset of the disease (1: 300). This titer was> 1: 10,000 before beginning treatment.

After taking blood and determining immunologically active parameters under optimal clinical conditions, IgY therapy ended after 6 months.

After discontinuation of the therapy for approximately 4 months, symptoms of a common swelling reappeared for the first time in late February 2012 (oral mucosal lesions and blisters of the skin on the upper part of the body). Non-specific joint pain and mild exhaustion symptoms preceded the recurrence of autoimmune disease.

Blood was taken again for analysis of autoantibodies and immunologically active parameters. The titers of specific autoantibodies rose only slightly (1: 400).

IgY treatment resumed. One bag of effervescent powder and 3 × 3 enteric tablets were administered per day (corresponding to the daily dose of about 8.4 g of the IgY agent of Preparation 2).

 Non-specific pain symptoms disappeared within a few days and the sores of the oral mucosa (slightly pronounced) healed quickly. No new blisters appeared on the skin and the old one healed within 14 days.

In this process, IgY  The healing effect of drugs on the overall symptoms of autoimmune disease has now been undoubtedly recognized.

After four months of therapy, disease relapse could be suppressed for the first time without the use of dexamethasone and mycophenolate mofetil.

Case 12:

Patient information: 41 years old, female

Duration of disease: 9 months (after bone marrow transplantation (BMT) due to leukemia)

Diagnosis:

Chronic graft-versus-host disease (GvHD).

History and local findings Local Findings ):

Nine months after BMT, chronic GvH and GvH keratitis were developed in the oral and genital mucosa. After a short time: Acute involvement of the lungs of GvH with general insufficiency of the lungs requiring ventilation. After surviving pulmonary GvH, long-term therapy was performed with prednisolone at a daily dose between 20 and 30 mg in addition to chemotherapy of leukemia. Cortisone administered gave a pronounced Cushing's disease syndrome.

 At doses of cortisone below 20 mg, chronic GvH in the mouth, eyes and vaginal mucosa was not reduced. The lungs currently have no effect, but are still severely limited in function.

From March / April 2011, oral IgY therapy was started with a daily dose of 2 teaspoons of powder in vanilla yoghurt (corresponding to about 2.5 g of the IgY drug of Preparation 2). Improvements in mouth and eye invasion have been observed, but genital GvH symptoms have not improved. The dose of prednisolone could be reduced to 15 mg daily dose (DD).

A "wash out" phase following a one month duration.

Intestinal IgY  Tablets and (optionally) IgY  Of effervescent powder Therapeutic  Individual treatment plan of the attempt.

The treatment plan provided, in the first month, the first dose of 3 × 3 enteric tablets (approximately 3.4 g of daily dose) per day for a duration of 4 weeks. In the first month, 270 enteric tablets of IgY were provided.

 All symptoms of GvH were recorded. Under consultation with oncologists and clinical findings, the dose of corticosteroids with immunosuppression could be reduced. In the case of clinical alleviation of GvH symptoms, therapy continued at the same dose until cortisone therapy gradually ceased completely. If the relief of symptoms is not complete or if it is necessary to maintain cortisone treatment, then further doses of effervescent powder were expected for the duration of 4 weeks. In the second month, 270 enteric tablets of IgY were provided.

The treatment plan also included the same dose of enteric tablets (3 × 3 tablets; about 3.4 g of Preparation 2 per day) to be administered for a duration of 4 weeks in the second month and 5 g of effervescent powder (Preparation 2 of IgY) Provide an additional dose of 2 x 1/2 bags (in each case based on the daily dose). The question of whether oral action will bring additional benefits for oral and possibly also conjunctival signs can be investigated. In the second month (and also in the third month), 30 bags of 270 enteric tablets and an optional IgY "foamable powder" are provided.

In the absence of an overall optimal action, the dose of enteric IgY tablets may be increased to 3 × 4 tablets (4.5 g of the daily dose of IgY agent of Preparation 2) for a duration of 4 weeks, leading to further foaming powder. Administration may only take place if there is a benefit. During the fourth month, 360 enteric tablets and 30 additional IgY "foamable powders" bags are provided.

If GvH is fully relieved without cortisone treatment for at least any one month period, the dose can be reduced to a maintenance dose of 3 × 1 tablets (daily dose) at weekly stages. The maintenance dose can then be determined again.

 The corner times of blood samples (also stool samples, if necessary) are as follows:

1. While enteric IgY tablets are administered, at the end of the "wash out" phase and before the beginning of the first 4-week period

2. After the first 4-week period

3. After discontinuation of cortisone

Mitigation occurs;

Clinical symptoms return when the dose is reduced.

In the case of a positive action, the patient can continue to receive the dose of medication as needed. If symptoms were fully relieved over a period of two months, discontinuation was attempted.

 GvH symptoms have been recorded by the patient since their inception in March 2011, with visual analogue scales (pain) and visible symptoms recorded by experts.

This was the first attempt of IgY therapy of chronic GvH.

The consequences of this personal healing attempt:

In April 2011, the first blood sample was already taken four weeks after the end of the testing phase with effervescent powder, due to the unexpected increase in tumor markers and the need for a connection to the rapid termination of cortisone treatment. At this point, cortisone treatment has already been discontinued and IgY therapy has begun and, unlike the original treatment strategy, immediately treated 3xx 4 tablets of enteric formulations in combination with a bag of effervescent powder.

 The rapid increase in tumor markers was a typical result of the high-dose cortisone treatment needed to inhibit GvHD. Cortisone inhibits the antitumor activity (inhibition of graft-to-tumor activity) of the donor bone marrow for the same dose, but not the graft-to-host response (GvHR).

Under this therapy, there was a continuous improvement of all disease symptoms of GvHD (despite the discontinuation of cortisone). Tumor markers could no longer be detected in the blood. Chemotherapy was therefore reduced in stages at the minimum dose. After 1 1/2 years, in August 2011, the patient resumed work, and in January 2012, with the ability almost completely re-established, blood was taken twice to analyze immunological activity parameters.

IgY therapy with effervescent powder in combination with enteric tablets continues while slowly decreasing the dose. If the good condition continues to be stable, complete termination of the tumor drug therapy is expected.

Case 13:

Patient information: 55 years old, male

Duration of illness: 18 months

Diagnosis:

1. Both chronic epicondylitis (right worse)

case history  And Local Findings :

The patient is a sports teacher, a swimming team trainer, and a sports therapist in physiotherapy work. Epicondylitis was restricted to the radial condyle on both sides for 18 months, initially only on the right side, and more severe on the right during the course of the next disease.

So far, treatment is done in orthopedics. Anti-inflammatory oral medications did not provide any relief. Topical injections of local anesthetics and cortisone sometimes resulted in relief that lasted for up to one day. Physiotherapy, tape and other assistive devices could not affect the progression of symptoms.

IgY Personal healing attempts by:

Individuals with IgY when pain at night no longer allows cohesive night sleep and when it is difficult to clench in the morning (both sides) in the morning for a one-hour duration and no longer guarantee that the patient is suitable for work Healing attempts have begun.

There were no other disease symptoms and this was the patient's first pain syndrome.

IgY therapy was started with an effervescent powder drug in 1 bag of daily dose (5 g of IgY drug in Preparation Example 2).

Symptom relief did not occur in the first treatment week.

In the second week only, there was a significant decrease in pain by about half of the first, and rarely awake at night due to pain at rest.

This improvement lasted about three weeks until pain increased again after upper respiratory tract infections (bronchitis, maxillary sinusitis). Thereafter, further IgY therapy was started with enteric tablets (dose of 2 × 4 tablets; corresponding to 3 g of IgY drug of Preparation Example 2).

Under this combination, virtually complete elimination of symptoms occurred for the first time. The patient woke up in the morning without stiffness of the fingers, reported that the full capacity of the lower arm muscles was returned and there was no night pain.

The remaining symptoms no longer appear daily, and the remaining symptoms are essentially the elbow's sensitivity to shock. If the therapy continues, the performance of the sport (cross-country skiing) is possible without limitation.

Two blood samples were taken and one analyzed the immunological activity parameters prior to the start of treatment and one with no significant symptoms.

Claims (10)

Polyneuropathy, mononeuropathy, autonomic neuropathy, fibrofibropathy, in particular in each case, autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E , F, G, H, multicellular group gamma globulin disease and / or the above symptoms in renal dysfunction
-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))
Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis
-Adjunctival disease in collagenoses
Achilles tendon pain
-Calcaneal pain and heel spur
Brachial scapular periarthritis
-Tyche syndrome (arthrosis of the clavicle joint)
Arthropathy of the sacroiliac joint
-Muscular arthrosis of the chewing organs, head jawbone dysfunction
Cervical spine syndrome after slowing trauma
Diverticulitis in colonic diverticulosis
Neurodermatitis
- asthma
-Interstitial cystitis (pain bladder syndrome)
-Food allergies
Allergies to light, especially polymorphic skin diseases
Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy
-Mucosal ulcers in Behcet's syndrome
-Mucosal erosion in the plain cloth window
-Mucosal lesions in scleroderma
-Mucosal lesions in Sjogren's syndrome
-Migraines without symptoms
Cardiovascular Disease
Drugs selected from the group consisting of antibodies, antibody fragments, insulin-like growth factor antagonists, toll-like receptor antagonists and mixtures thereof for the treatment or prevention of diseases anatomically pathologically correlated with a disease selected from the group consisting of:
In the case of asthma above, the drug does not include insulin-like growth factor antagonists and toll-like receptor antagonists,
(i.) the treatment or prevention is performed orally and / or
(ii.) The antibody and / or antibody fragment targets at least 5 wt.%, preferably 10 wt.% of Gram negative bacteria relative to the total antibody content of the drug.
The drug of claim 1, wherein the treatment or prophylaxis is performed orally.
The drug of claim 1, wherein the antibody and / or antibody fragment is targeted to Gram negative bacteria.
The drug of claim 1, wherein the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist is at least partially derived from algae.
The drug according to any one of the preceding claims, wherein the drug is a component of a medicament and / or a formulation prepared for administration.
The drug of claim 1, wherein the antibody, antibody fragment, insulin-like growth factor antagonist and / or toll-like receptor antagonist is at least partially derived from a chicken.
6. A drug according to claim 5 for treating or preventing colostrum.
The method according to any one of the preceding claims, characterized in that the treatment or prevention is carried out by the daily dose of the preparation prepared for the administration of 1.0-10.0 g, preferably 2.0-8.0 g, more preferably 2.5-7.5 g. Drugs for treatment or prevention.
The drug of claim 1, wherein the treatment or prophylaxis is carried out by daily administration for 4-14 weeks, preferably 8-12 weeks.
Polyneuropathy, mononeuropathy, autonomic neuropathy, fibrofibropathy, in particular in each case, autoimmune diseases, type 1 and type 2 diabetes, diabetes type A, B, C, D, E , F, G, H, multicellular group gamma globulin disease and / or the above symptoms in renal dysfunction
-Peripheral nerve compression syndrome (e.g., carpal tunnel syndrome), autologous seizures syndrome (phallus tunnel syndrome, Molton neuroma, Bernardos syndrome (dysceptive thigh neuralgia), thoracic outlet syndrome (TOS))
Arthrosis other than osteoarthritis, especially activated arthrosis, primary arthrosis, secondary arthrosis
-Adjunctival disease in collagenoses
-Lateral epicondylitis
Achilles tendon pain
-Calcaneal pain and heel spur
Brachial scapular periarthritis
-Tyche syndrome (arthrosis of the clavicle joint)
Arthropathy of the sacroiliac joint
-Muscular arthrosis of the chewing organs, head jawbone dysfunction
Cervical spine syndrome after slowing trauma
Diverticulitis in colonic diverticulosis
Neurodermatitis
- asthma
-Interstitial cystitis (pain bladder syndrome)
-Food allergies
Allergies to light, especially polymorphic skin diseases
Mucositis, in particular, oral mucositis and / or mucositis after radiotherapy (radioactive mucositis) and / or mucositis after chemotherapy and / or under chemotherapy
-Mucosal ulcers in Behcet's syndrome
-Mucosal erosion in the plain cloth window
-Mucosal lesions in scleroderma
-Mucosal lesions in Sjogren's syndrome
-Migraines without symptoms
Cardiovascular Disease
Irritable bowel syndrome
-Reactive arthritis
-Ulcerative colitis
Crohn's disease
Graft versus host disease
In the treatment or prevention of a disease anatomically pathologically correlated with a disease selected from the X and Y groups, the antibody for treating or preventing the disease by promoting apoptosis of mononuclear cells that swallow lipopolysaccharide. , A drug selected from the group consisting of antibody fragments, insulin like growth factor antagonists, toll like receptor antagonists and mixtures thereof.

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